Detection of IDH2 Mutations and Monitoring Molecular Residual Disease in Patients With AML

Detection of IDH2 Mutations and Monitoring Molecular Residual Disease in Patients With Acute Myeloid Leukemia

1. Detection of IDH2 mutations in AML patients to define it incidence and correlation with clinical characteristics, relapse-free and overall survival.
2. Identify AML patients who are potential candidates for IDH2 inhibitor treatment.
3. Monitoring minimal residual disease (MRD) following therapy to evaluate its possible role in the strategy of MRD-directed therapy in the future in patients carrying IDH2 mutations at initial diagnosis.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia

Detailed Description

Isocitrate dehydrogenase 2 (IDH2) was found to be one of the recurrently mutated genes in acute myeloid leukemia, indicating its critical role in leukemogenesis. IDH2 mutations account for about 10%-20% of AML patients. IDH2 mutation is found to be associated with production of 2-HG, which interferes with histone methylation and DNA modification, results in partial block of myeloid cell differentiation. IDH inhibitors have shown in preclinical model to reverse differentiation blockage in tumor cells. The assessment of IDH2 inhibitors is ongoing with phase I/II clinical trials. The analysis of IDH2 mutation in AML patients will help to identify AML patients who might benefit from IDH inhibitor treatment.

Bone marrow samples from 300 adult patients (>20 years old) with newly diagnosed AML since 2014/1/1 and received standard chemotherapy in hospitals which has jointed Ministry of Health and Welfare AML program will be examined. The mononuclear cells are extracted from bone marrow samples at the initial diagnosis. The mutational analysis of exon 4 of IDH2 gene will be performed by PCR amplication followed by pyrosequencing to detect IDH2-R140 and R172 mutations and mutant levels. Follow-up samples of patients carrying IDH2 mutations at the time of achieving hematologic remission, subsequent samples during different time points including at least following two post-remission chemotherapy, at the end of therapy and every 3 months thereafter in the first year and then every 6 months up to 24 months, as well as at time of relapse, will be measured by LNA-quantitative real-time PCR with TaqMan probe assay to determine the changes of IDH2 mutant levels.

• Study Type: Observational
• Enrollment (Actual): 334

Contacts and Locations

Study Locations

• Taiwan
  • State
    • Taoyuan, State, Taiwan, 33305
      • Chang Gung Memorial Hospital-Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with AML newly diagnosed and followed in Chang Gung Memorial Hospital.

Description

Inclusion Criteria:

• Patients diagnosed with AML, age ≥ 20 years, and are willing to sign the informed consent

Exclusion Criteria:

• Not AML patients
• Patients diagnosed with AML but age < 20 years

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of IDH2 mutations	The mononuclear cells will be extracted from bone marrow samples at the initial diagnosis. The mutational analysis of exon 4 of IDH2 gene will be performed by PCR amplication followed by pyrosequencing to detect IDH2-R140 and R172 mutations and mutant levels.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follow-up detection of IDH2 mutations	Follow-up samples of patients carrying IDH2 mutations at the time of achieving hematologic remission, subsequent samples during different time points including at least following two post-remission chemotherapy, at the end of therapy and every 3 months thereafter in the first year and then every 6 months up to 24 months, as well as at time of relapse, will be measured by LNA-quantitative real-time PCR with TaqMan probe assay to determine the changes of IDH2 mutant levels.	24 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Lee-Yung Shih, MD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 201700154B0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No